Abstract

Background

Approximately 50% of patients with major depressive disorder (MDD) do not respond
optimally to antidepressant treatments. Given this is a large proportion of the patient
population, pretreatment tests that predict which patients will respond to which types
of treatment could save time, money and patient burden. Brain imaging offers a means
to identify treatment predictors that are grounded in the neurobiology of the treatment
and the pathophysiology of MDD.

Methods/Design

The international Study to Predict Optimized Treatment in Depression is a multi-center,
parallel model, randomized clinical trial with an embedded imaging sub-study to identify
such predictors. We focus on brain circuits implicated in major depressive disorder
and its treatment. In the full trial, depressed participants are randomized to receive
escitalopram, sertraline or venlafaxine-XR (open-label). They are assessed using standardized
multiple clinical, cognitive-emotional behavioral, electroencephalographic and genetic
measures at baseline and at eight weeks post-treatment. Overall, 2,016 depressed participants
(18 to 65 years old) will enter the study, of whom a target of 10% will be recruited
into the brain imaging sub-study (approximately 67 participants in each treatment
arm) and 67 controls. The imaging sub-study is conducted at the University of Sydney
and at Stanford University. Structural studies include high-resolution three-dimensional
T1-weighted, diffusion tensor and T2/Proton Density scans. Functional studies include
standardized functional magnetic resonance imaging (MRI) with three cognitive tasks
(auditory oddball, a continuous performance task, and Go-NoGo) and two emotion tasks
(unmasked conscious and masked non-conscious emotion processing tasks). After eight
weeks of treatment, the functional MRI is repeated with the above tasks. We will establish
the methods in the first 30 patients. Then we will identify predictors in the first
half (n = 102), test the findings in the second half, and then extend the analyses
to the total sample.